Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Sexual Health Sexual Health Society
Publishing on sexual health from the widest perspective
RESEARCH ARTICLE

HIV infection and bone disease: implications for an aging population

Aoife G. Cotter A B C and Patrick W. G. Mallon A B
+ Author Affiliations
- Author Affiliations

A HIV Molecular Research Group, School of Medicine & Medical Science, University College Dublin 7, Ireland.

B Department of Infectious Diseases, Mater Misericordiae University Hospital, Dublin 7, Ireland.

C Corresponding author. Email: Aoife.cotter@ucdconnect.ie

Sexual Health 8(4) 493-501 https://doi.org/10.1071/SH11014
Submitted: 4 February 2011  Accepted: 27 June 2011   Published: 30 September 2011

Abstract

Now more than ever, the management of age-related problems, from cardiovascular morbidity to bone pathology, is increasingly relevant for HIV physicians. Low bone mineral density (BMD) and fractures are more common in HIV-infected patients. Although a multifactorial aetiology underlies this condition, increasing evidence suggests a role for antiretroviral therapy in low BMD, especially upon initiation. This review will detail the epidemiology, pathogenesis, diagnosis and management of osteoporosis and low BMD in HIV-infected patients, with particular emphasis on aging.

Additional keywords: antiretroviral therapy, bone mineral density, osteopaenia, osteoporosis.


References

[1]  Martin CP, Fain MJ, Klotz SA. The older HIV-positive adult: a critical review of the medical literature. Am J Med 2008; 121 1032–7.
The older HIV-positive adult: a critical review of the medical literature.Crossref | GoogleScholarGoogle Scholar |

[2]  Bhavan KP, Kampalath VN, Overton ET. The aging of the HIV epidemic. Curr HIV/AIDS Rep 2008; 5 150–8.
The aging of the HIV epidemic.Crossref | GoogleScholarGoogle Scholar |

[3]  Effros RB, Fletcher CV, Gebo K, Halter JB, Hazzard WR, Horne FM, et al Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions. Clin Infect Dis 2008; 47 542–53.
Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions.Crossref | GoogleScholarGoogle Scholar |

[4]  Consensus Development Conference Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993; 94 646–50.
Diagnosis, prophylaxis, and treatment of osteoporosis.Crossref | GoogleScholarGoogle Scholar |

[5]  Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994; 4 368–81.
Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M3htVyktA%3D%3D&md5=02dd3e6263441534fac984e0f42c7afaCAS |

[6]  National Osteoporosis Foundation (NOF). America’s bone health: the state of osteoporosis and low bone mass in our nation. Washington, DC: NOF; 2002.

[7]  Mackey DC, Lui LY, Cawthon PM, Bauer DC, Nevitt MC, Cauley JA, et al High-trauma fractures and low bone mineral density in older women and men. JAMA 2007; 298 2381–8.
High-trauma fractures and low bone mineral density in older women and men.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlyjtL3N&md5=ebf2ff913c5f369edbf1a85fc671197bCAS |

[8]  Poole KE, Compston JE. Osteoporosis and its management. BMJ 2006; 333 1251–6.
Osteoporosis and its management.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1Siur0%3D&md5=4b2108b91bb9bb4df826a0fa9b3dd177CAS |

[9]  Mellström D, Vandenput L, Mallmin H, Holmberg AH, Lorentzon M, Oden A, et al Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res 2008; 23 1552–60.
Older men with low serum estradiol and high serum SHBG have an increased risk of fractures.Crossref | GoogleScholarGoogle Scholar |

[10]  LeBlanc ES, Nielson CM, Marshall LM, Lapidus JA, Barrett-Connor E, Ensrud KE, et al The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. J Clin Endocrinol Metab 2009; 94 3337–46.
The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFCht7fK&md5=d1a4ab90bae89e1a01e81865441cc64aCAS |

[11]  Cummings SR, Cawthon PM, Ensrud KE, Cauley JA, Fink HA, Orwoll ES. BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women. J Bone Miner Res 2006; 21 1550–6.
BMD and risk of hip and nonvertebral fractures in older men: a prospective study and comparison with older women.Crossref | GoogleScholarGoogle Scholar |

[12]  Seeman E. Structural basis of growth-related gain and age-related loss of bone strength. Rheumatology 2008; 47 iv2–8.
Structural basis of growth-related gain and age-related loss of bone strength.Crossref | GoogleScholarGoogle Scholar |

[13]  Fitzpatrick LA. Secondary causes of osteoporosis. Mayo Clin Proc 2002; 77 453–68.
Secondary causes of osteoporosis.Crossref | GoogleScholarGoogle Scholar |

[14]  van Staa TP, Dennison EM, Leufkens HG, Cooper C. Epidemiology of fractures in England and Wales. Bone 2001; 29 517–22.
Epidemiology of fractures in England and Wales.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3Mnot1equg%3D%3D&md5=bcee82732d4f43d9f3ba3e4f4875d265CAS |

[15]  Johnell O, Borgstrom F, Jonsson B, Kanis J. Latitude, socioeconomic prosperity, mobile phones and hip fracture risk. Osteoporos Int 2007; 18 333–7.
Latitude, socioeconomic prosperity, mobile phones and hip fracture risk.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2s%2FoslOmsw%3D%3D&md5=05e8550dc5ad1b7560f65f9213b6253dCAS |

[16]  Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 2009; 301 513–21.
Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtlyqs7Y%3D&md5=c6190b1fc0f55bbeacf514d09f9d1bccCAS |

[17]  U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: U.S. Department of Health and Human Services, Office of the Surgeon General; 2004.

[18]  National Osteoporosis Foundation (NOF). Clinician’s guide to prevention and treatment of osteoporosis. Washington, DC: NOF; 2010.

[19]  National Osteoporosis Society (NOS). Osteoporosis facts and figures. NOS; 2006. Available online at: http://www.nos.org.uk/page.aspx?pid=328 [verified July 2011].

[20]  Libois A, Clumeck N, Kabeya K, Gerard M, De Wit S, Poll B, et al Risk factors of osteopenia in HIV-infected women: no role of antiretroviral therapy. Maturitas 2010; 65 51–4.
Risk factors of osteopenia in HIV-infected women: no role of antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3c%2Fos1SjtQ%3D%3D&md5=2f5ca3cd8062d75e9d272c4e568f4ebaCAS |

[21]  Calmy A, Fux CA, Norris R, Vallier N, Delhumeau C, Samaras K, et al Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. J Infect Dis 2009; 200 1746–54.
Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsFOlsrrJ&md5=8dcab5dc0a1820e503e72e2bebf7e2d8CAS |

[22]  Duvivier C, Kolta S, Assoumou L, Ghosn J, Rozenberg S, Murphy RL, et al Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients. AIDS 2009; 27 817–24.
Greater decrease in bone mineral density with protease inhibitor regimens compared with nonnucleoside reverse transcriptase inhibitor regimens in HIV-1 infected naive patients.Crossref | GoogleScholarGoogle Scholar |

[23]  Madeddu G, Spanu A, Chessa F, Calia GM, Lovigu C, Mannazzu M, et al Serum leptin and bone metabolism in HIV patients treated with highly active antiretroviral therapy. Q J Nucl Med Mol Imaging 2009; 53 290–301.

[24]  Tomazic J, Ul K, Volcansek G, Gorensek S, Pfeifer M, Karner P, et al Prevalence and risk factors for osteopenia/osteoporosis in an HIV-infected male population. Wien Klin Wochenschr 2007; 119 639–46.
Prevalence and risk factors for osteopenia/osteoporosis in an HIV-infected male population.Crossref | GoogleScholarGoogle Scholar |

[25]  Brown TT, Ruppe MD, Kassner R, Kumar P, Kehoe T, Dobs AS, et al Reduced bone mineral density in human immunodeficiency virus-infected patients and its association with increased central adiposity and postload hyperglycemia. J Clin Endocrinol Metab 2004; 89 1200–6.
Reduced bone mineral density in human immunodeficiency virus-infected patients and its association with increased central adiposity and postload hyperglycemia.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXisVWrurc%3D&md5=30145b79a981de3016f3b87a1d66e24eCAS |

[26]  Mondy K, Yarasheski K, Powderly WG, Whyte M, Claxton S, DeMarco D, et al Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals. Clin Infect Dis 2003; 36 482–90.
Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals.Crossref | GoogleScholarGoogle Scholar |

[27]  Moore AL, Vashisht A, Sabin CA, Mocroft A, Madge S, Phillips AN, et al Reduced bone mineral density in HIV-positive individuals. AIDS 2001; 15 1731–3.
Reduced bone mineral density in HIV-positive individuals.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3Mvpsl2msw%3D%3D&md5=0c096a721b85f55ca543062cd12afa17CAS |

[28]  Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Santoro N, Schoenbaum EE. HIV infection and bone mineral density in middle-aged women. Clin Infect Dis 2006; 42 1014–20.
HIV infection and bone mineral density in middle-aged women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xjtlelt7k%3D&md5=e3a079e0289b56f7795cf2877f7d8986CAS |

[29]  Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Lo Y, Klein RS. Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection. AIDS 2007; 21 617–23.
Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection.Crossref | GoogleScholarGoogle Scholar |

[30]  Dolan SE, Huang JS, Killilea KM, Sullivan MP, Aliabadi N, Grinspoon S. Reduced bone density in HIV-infected women. AIDS 2004; 18 475–83.
Reduced bone density in HIV-infected women.Crossref | GoogleScholarGoogle Scholar |

[31]  Bruera D, Luna N, David DO, Bergoglio LM, Zamudio J. Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy. AIDS 2003; 17 1917–23.
Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy.Crossref | GoogleScholarGoogle Scholar |

[32]  Fausto A, Bongiovanni M, Cicconi P, Menicagli L, Ligabo EV, Melzi S, et al Potential predictive factors of osteoporosis in HIV-positive subjects. Bone 2006; 38 893–7.
Potential predictive factors of osteoporosis in HIV-positive subjects.Crossref | GoogleScholarGoogle Scholar |

[33]  Breen EC, Rezai AR, Nakajima K, Beall GN, Mitsuyasu RT, Hirano T, et al Infection with HIV is associated with elevated IL-6 levels and production. J Immunol 1990; 144 480–4.
| 1:CAS:528:DyaK3cXhtlOiu7o%3D&md5=4e1124585d41238f05f37fd37f7812b7CAS |

[34]  Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 1995; 332 305–11.
Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2M7hsFOiuw%3D%3D&md5=73bf9556a90259949f9200a3fca612dbCAS |

[35]  Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 2006; 20 2165–74.
Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review.Crossref | GoogleScholarGoogle Scholar |

[36]  Bolland MJ, Grey AB, Gamble GD, Reid IR. Clinical review: low body weight mediates the relationship between HIV infection and low bone mineral density: a meta-analysis. J Clin Endocrinol Metab 2007; 92 4522–8.
Clinical review: low body weight mediates the relationship between HIV infection and low bone mineral density: a meta-analysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmslWhtr0%3D&md5=6368a056da94914fd243b0740cfcbf02CAS |

[37]  Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, Miller MD, et al Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. JAMA 2004; 292 191–201.
Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXlvVSnur0%3D&md5=79b4b813eef3fb21b477d42117956afeCAS |

[38]  van Vonderen MG, Lips P, van Agtmael MA, Hassink EA, Brinkman K, Geerlings SE, et al First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir. AIDS 2009; 23 1367–76.
First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnsl2gsLs%3D&md5=c1ee717c438aab3ecd809b66ab887307CAS |

[39]  Stellbrink HJ, Orkin C, Arribas JR, Compston J, Gerstoft J, Van Wijngaerden E, et al Comparison of changes in bone density and turnover with abacavir–lamivudine versus tenofovir–emtricitabine in HIV-infected adults: 48-week results from the ASSERT study. Clin Infect Dis 2010; 51 963–72.
Comparison of changes in bone density and turnover with abacavir–lamivudine versus tenofovir–emtricitabine in HIV-infected adults: 48-week results from the ASSERT study.Crossref | GoogleScholarGoogle Scholar |

[40]  McComsey G, Kitch D, Daar E, Tierney C, Jahed N, Tebas P, et al. Bone and limb fat outcomes of ACTG A5224s, a substudy of ACTG A5202: a prospective, randomized, partially blinded phase III trial of ABC/3TC or TDF/FTC with EFV or ATV/r for initial treatment of HIV-1 infection. 17th Conference on Retroviruses and Opportunistic Infections; 2010 Feb 16–19; San Francisco.

[41]  Martin A, Amin J, Cooper DA, Carr A, Kelleher AD, Bloch M, et al Abacavir does not affect circulating levels of inflammatory or coagulopathic biomarkers in suppressed HIV: a randomized clinical trial. AIDS 2010; 24 2657–63.
Abacavir does not affect circulating levels of inflammatory or coagulopathic biomarkers in suppressed HIV: a randomized clinical trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtlGmt7bO&md5=ad381dc8e410de435ec494def9303b00CAS |

[42]  European Centre for Disease Prevention and Control. Annual epidemiological report in communicable diseases in Europe, 2008. Stockholm: European Centre for Disease Prevention and Control; 2008.

[43]  Gafni RI, Hazra R, Reynolds JC, Maldarelli F, Tullio AN, DeCarlo E, et al Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children. Pediatrics 2006; 118 e711–8.
Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children.Crossref | GoogleScholarGoogle Scholar |

[44]  Önen NF, Overton ET, Seyfried W, Stumm ER, Snell M, Mondy K, et al Aging and HIV infection: a comparison between older HIV-infected persons and the general population. HIV Clin Trials 2010; 11 100–9.
Aging and HIV infection: a comparison between older HIV-infected persons and the general population.Crossref | GoogleScholarGoogle Scholar |

[45]  Sharma A, Flom PL, Weedon J, Klein RS. Prospective study of bone mineral density changes in aging men with or at risk for HIV infection. AIDS 2010; 24 2337–45.

[46]  Yin MT, McMahon DJ, Ferris DC, Zhang CA, Shu A, Staron R, et al Low bone mass and high bone turnover in postmenopausal human immunodeficiency virus-infected women. J Clin Endocrinol Metab 2010; 95 620–9.
Low bone mass and high bone turnover in postmenopausal human immunodeficiency virus-infected women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitVaisrc%3D&md5=fd7bc4c1c9537382f2005e6b6bafeb60CAS |

[47]  Yin M, Dobkin J, Brudney K, Becker C, Zadel JL, Manandhar M, et al Bone mass and mineral metabolism in HIV+ postmenopausal women. Osteoporos Int 2005; 16 1345–52.
Bone mass and mineral metabolism in HIV+ postmenopausal women.Crossref | GoogleScholarGoogle Scholar |

[48]  Triant VA, Brown TT, Lee H, Grinspoon SK. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab 2008; 93 3499–504.
Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFChurnE&md5=ce7b5c59a408ce0e1aaa7dfd936626cbCAS |

[49]  Young B, Dao CN, Buchacz K, Baker R, Brooks JT. Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000–2006. Clin Infect Dis 2011; 52 1061–8.
Increased rates of bone fracture among HIV-infected persons in the HIV Outpatient Study (HOPS) compared with the US general population, 2000–2006.Crossref | GoogleScholarGoogle Scholar |

[50]  Collin F, Duval X, Le Moing V, Piroth L, Al Kaied F, Massip P, et al Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults. AIDS 2009; 23 1021–4.
Ten-year incidence and risk factors of bone fractures in a cohort of treated HIV1-infected adults.Crossref | GoogleScholarGoogle Scholar |

[51]  Womack JA, Goulet JL, Gibert C, Brandt C, Chang CC, Gulanski B, et al Increased risk of fragility fractures among HIV infected compared to uninfected male veterans. PLoS ONE 2011; 6 e17217
Increased risk of fragility fractures among HIV infected compared to uninfected male veterans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXislCgs70%3D&md5=59c8239da0fba40a14caaedfb05bca35CAS |

[52]  Kanis JA, Burlet N, Cooper C, Delmas PD, Reginster JY, Borgstrom F, et al European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2008; 19 399–428.
European guidance for the diagnosis and management of osteoporosis in postmenopausal women.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1c3itFekuw%3D%3D&md5=c6f05925be4a15dd9e06bb995591352fCAS |

[53]  Gazzola L, Comi L, Savoldi A, Tagliabue L, Del Sole A, Pietrogrande L, et al Use of the FRAX equation as first-line screening of bone metabolism alteration in the HIV-infected population. J Infect Dis 2010; 202 330–1.
Use of the FRAX equation as first-line screening of bone metabolism alteration in the HIV-infected population.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3crhs12qtA%3D%3D&md5=53417a89ae1bd65941632443a4d8b8e5CAS |

[54]  European AIDS Clinical Society. EACS prevention and management of non-infectious co-morbidities in HIV. EACS; 2009. Available online at: http://www.europeanaidsclinicalsociety.org/Guidelines/G2.htm [verified July 2011].

[55]  McComsey GA, Tebas P, Shane E, Yin MT, Overton ET, Huang JS, et al Bone disease in HIV infection: a practical review and recommendations for HIV care providers. Clin Infect Dis 2010; 51 937–46.
Bone disease in HIV infection: a practical review and recommendations for HIV care providers.Crossref | GoogleScholarGoogle Scholar |

[56]  Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, et al HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci 2007; 62 1279–86.

[57]  Desquilbet L, Margolick JB, Fried LP, Phair JP, Jamieson BD, Holloway M, et al Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr 2009; 50 299–306.
Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men.Crossref | GoogleScholarGoogle Scholar |

[58]  Önen NF, Agbebi A, Shacham E, Stamm KE, Onen AR, Overton ET. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect 2009; 59 346–52.
Frailty among HIV-infected persons in an urban outpatient care setting.Crossref | GoogleScholarGoogle Scholar |

[59]  Terzian AS, Holman S, Nathwani N, Robison E, Weber K, Young M, et al Factors associated with preclinical disability and frailty among HIV-infected and HIV-uninfected women in the era of cART. J Womens Health (Larchmt) 2009; 18 1965–74.
Factors associated with preclinical disability and frailty among HIV-infected and HIV-uninfected women in the era of cART.Crossref | GoogleScholarGoogle Scholar |

[60]  Cooper RD, Wiebe N, Smith N, Keiser P, Naicker S, Tonelli M. Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients. Clin Infect Dis. 2010; 51 496–505.
Systematic review and meta-analysis: renal safety of tenofovir disoproxil fumarate in HIV-infected patients.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFyiu7%2FM&md5=b577cdc4da20a472a55cb3b15fdb718bCAS |

[61]  Holick MF. Vitamin D deficiency. N Engl J Med 2007; 357 266–81.
Vitamin D deficiency.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotVejsbc%3D&md5=8215adefff46b7f9e11c22f03ceb313bCAS |

[62]  Welz T, Childs K, Ibrahim F, Poulton M, Taylor CB, Moniz CF, et al Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase. AIDS 2010; 24 1923–8.
Efavirenz is associated with severe vitamin D deficiency and increased alkaline phosphatase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXos1WqtrY%3D&md5=27b796c7ed7b66255734a6d56e26d7efCAS |

[63]  Haug CJ, Aukrust P, Haug E, Morkrid L, Muller F, Froland SS. Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis. J Clin Endocrinol Metab 1998; 83 3832–8.
Severe deficiency of 1,25-dihydroxyvitamin D3 in human immunodeficiency virus infection: association with immunological hyperactivity and only minor changes in calcium homeostasis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXntlOisb0%3D&md5=38c8d381bb836bde1c936ca974b2863cCAS |

[64]  Stephensen CB, Marquis GS, Kruzich LA, Douglas SD, Aldrovandi GM, Wilson CM. Vitamin D status in adolescents and young adults with HIV infection. Am J Clin Nutr 2006; 83 1135–41.
| 1:CAS:528:DC%2BD28XkvFOrtr4%3D&md5=99c8e45a9ea935fa6f5109bc7b56ef6aCAS |

[65]  Dawson-Hughes B, Mithal A, Bonjour JP, Boonen S, Burckhardt P, Fuleihan GE, et al IOF position statement: vitamin D recommendations for older adults. Osteoporos Int 2010; 21 1151–4.
IOF position statement: vitamin D recommendations for older adults.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3cnotF2jtw%3D%3D&md5=52e96d04e5980909af72a2d405cde674CAS |

[66]  Ross AC. The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr 2011; 14 938–9.
The 2011 report on dietary reference intakes for calcium and vitamin D.Crossref | GoogleScholarGoogle Scholar |

[67]  Trang HM, Cole DE, Rubin LA, Pierratos A, Siu S, Vieth R. Evidence that vitamin D3 increases serum 25-hydroxyvitamin D more efficiently than does vitamin D2. Am J Clin Nutr 1998; 68 854–8.
| 1:CAS:528:DyaK1cXmsV2gs78%3D&md5=743b198064f4cba9809ae78a9a8607eeCAS |

[68]  Adams JS, Hewison M. Update in vitamin D. J Clin Endocrinol Metab 2010; 95 471–8.
Update in vitamin D.Crossref | GoogleScholarGoogle Scholar |

[69]  Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96 1911–30.
Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXptlSku7o%3D&md5=7bef8ecf3324b9732170dc8dcc1d5116CAS |

[70]  Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, et al Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 1996; 348 1535–41.
Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXisFCktQ%3D%3D&md5=e204daf780a3a1b7817fcf0fa57b1bc4CAS |

[71]  Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, et al Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 1999; 282 1344–52.
Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmvFansr0%3D&md5=7cb912be89ac783cffa7c8b7648e5515CAS |

[72]  Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, et al Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356 1809–22.
Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXltVSktLc%3D&md5=3e225df3da34f302c40f285f5b16295eCAS |

[73]  Guaraldi G, Orlando G, Madeddu G, Vescini F, Ventura P, Campostrini S, et al Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis. HIV Clin Trials 2004; 5 269–77.
Alendronate reduces bone resorption in HIV-associated osteopenia/osteoporosis.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2crovVahsQ%3D%3D&md5=6e8d063779b99b86c7df569f380a64cfCAS |

[74]  Mondy K, Powderly WG, Claxton SA, Yarasheski KH, Royal M, Stoneman JS, et al Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection. J Acquir Immune Defic Syndr 2005; 38 426–31.
Alendronate, vitamin D, and calcium for the treatment of osteopenia/osteoporosis associated with HIV infection.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXit1ekt7Y%3D&md5=55c230f7433c20d089e13fb896ada606CAS |

[75]  Negredo E, Martinez-Lopez E, Paredes R, Rosales J, Perez-Alvarez N, Holgado S, et al Reversal of HIV-1-associated osteoporosis with once-weekly alendronate. AIDS 2005; 19 343–5.
| 1:CAS:528:DC%2BD2MXhsVymtb4%3D&md5=08f459f1390f4ec7f48dcc8bb363061eCAS |

[76]  McComsey GA, Kendall MA, Tebas P, Swindells S, Hogg E, Alston-Smith B, et al Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV. AIDS 2007; 21 2473–82.
Alendronate with calcium and vitamin D supplementation is safe and effective for the treatment of decreased bone mineral density in HIV.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlWjtL3P&md5=cc19a66f98a17bda3fce2a5607ac2956CAS |

[77]  Bolland MJ, Grey AB, Horne AM, Briggs SE, Thomas MG, Ellis-Pegler RB, et al Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial. J Clin Endocrinol Metab 2007; 92 1283–8.
Annual zoledronate increases bone density in highly active antiretroviral therapy-treated human immunodeficiency virus-infected men: a randomized controlled trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksVSrsbk%3D&md5=f063121b428d0b421ba25e939fb4911eCAS |

[78]  Fairfield WP, Finkelstein JS, Klibanski A, Grinspoon SK. Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome. J Clin Endocrinol Metab 2001; 86 2020–6.
Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjs1Omsbc%3D&md5=7db5c2116e15a82d7f7fd13b53f1edbeCAS |

[79]  Dolan Looby SE, Collins M, Lee H, Grinspoon S. Effects of long-term testosterone administration in HIV-infected women: a randomized, placebo-controlled trial. AIDS 2009; 23 951–9.
Effects of long-term testosterone administration in HIV-infected women: a randomized, placebo-controlled trial.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltlKqs74%3D&md5=bd48cfd9c907790078c7e1ed5174b7c8CAS |

[80]  Konishi M, Takahashi K, Yoshimoto E, Uno K, Kasahara K, Mikasa K. Association between osteopenia/osteoporosis and the serum RANKL in HIV-infected patients. AIDS 2005; 19 1240–1.
Association between osteopenia/osteoporosis and the serum RANKL in HIV-infected patients.Crossref | GoogleScholarGoogle Scholar |

[81]  Martin ME, Benassayag C, Amiel C, Canton P, Nunez EA. Alterations in the concentrations and binding properties of sex steroid binding protein and corticosteroid-binding globulin in HIV+ patients. J Endocrinol Invest 1992; 15 597–603.
| 1:CAS:528:DyaK3sXhvV2ktL0%3D&md5=4bd153fb2bd0f17926c2571b785a785fCAS |

[82]  Mallon PW. HIV and bone mineral density. Curr Opin Infect Dis 2010; 23 1–8.
HIV and bone mineral density.Crossref | GoogleScholarGoogle Scholar |

[83]  Faulkner KG, Wacker WK, Barden HS, Simonelli C, Burke PK, Ragi S, et al Femur strength index predicts hip fracture independent of bone density and hip axis length. Osteoporos Int 2006; 17 593–9.
Femur strength index predicts hip fracture independent of bone density and hip axis length.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD287msF2muw%3D%3D&md5=2c4d1dd2d552e449d6f50c2455c42123CAS |